Cell division is a basic process for developing and growing living organisms, needless to say, which is the most dynamic behavior in a biological cell cycle. It is widely known that abnormal regulation of cell division leads to “malignant alteration”. Cell division is a very important process but still many points remain unexplained. One of these points (riddles) is synchronized motion of chromosomes that momentarily occurs and observed in cell division.
It has been known for 100 years or more that the number of chromosomes of a cancer cell differs from that of a normal cell. It has been also known that the number of chromosomes of a cancer cell easily varies, and that cancer cells having different number of chromosomes are produced in a cancer-cell proliferation. Such variation in the number of chromosomes, in other words, chromosomal instability, contributes to diversity of cancer cells, furthermore, a high grade of malignancy. The diversity of cancer cells constituting a tumor is the biggest factor that makes it difficult to treat cancer. In other words, due to the presence of diversified cancer cells different in resistance to an anticancer agent, it difficult to kill all cancer cells.
From the above background, analyzing a molecular mechanism underlying chromosomal instability may lead to develop a new treatment of cancer. From the expectation, attention has been focused on importance of genes involved in cohesion or segregation of sister chromatids. In particular, overexpression of separase, which is a protease cleaving an adhesion factor called cohesin present between sister chromatids, and securin, which is a one of regulatory factor for separase, has been reported to cause chromosomal instability, leading to canceration of the cell. Overexpression of separase and securin is considered as a significant factor in the “malignant alteration” process.
Basically, in the progression process of a normal cell division, segregation of sister chromatids is an important event and strictly controlled. In the segregation of sister chromatids, two events, i.e., removal of cohesin and poleward movement of chromatids, are controlled to simultaneously proceed (Non Patent Literatures 1, 2).
The former is started when cohesin, a protein complex that holds sister chromatids together, is decomposed by the protease separase (Non Patent Literatures 3, 4). Separase is known to be activated by control of securin (Non Patent Literatures 5-7).
The latter involves proteins that regulate microtubule, including kinesins that promote microtubule depolymerization (Non Patent Literature 8), and chromokinesins (Non Patent Literature 9). Little is known about the mechanism that controls these proteins, but it is said that the mechanism depends on a decrease in cyclin-dependent kinase (Cdk1) activity (Non Patent Literatures 9-11).
It is considered that the two processes, i.e., removal of cohesin and poleward movement of chromosomes are cooperatively, orderly and strictly controlled, in consideration that all chromosomes segregate and move poleward in an extremely short time.